Dwivedi Ashish Ranjan, Kumar Vijay, Prashar Vikash, Jangid Kailash, Kumar Naveen, Devi Bharti, Parkash Jyoti, Kumar Vinod
Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab Bathinda Punjab 151401 India.
Laboratory of Organic and Medicinal Chemistry, Department of Chemistry, Central University of Punjab Bathinda Punjab 151401 India
RSC Med Chem. 2025 Jan 15. doi: 10.1039/d4md00755g.
Twelve 2,4-bis-substituted quinazoline-based compounds were synthesized and screened for antiproliferative and tubulin polymerization enhancing potential. In the series, compound A4V-3 substituted with an imidazole ring displayed IC values of 4.25 μM, 2.65 μM, and 9.95 μM, and A4V-5 with a benzotriazole substitution displayed IC values of 3.45 μM, 7.25 μM, and 8.14 μM against MCF-7, HCT-116 and SHSY-5Y cancer cells, respectively. In the mechanistic studies involving cell cycle analysis, apoptosis assay and JC-1 studies, compound A4V-3 was found to arrest the cells in the G/M phase of the cell cycle and induce mitochondria-mediated apoptosis. In addition, compound A4V-3 displayed significant tubulin polymerization-enhancing potential. 2,4-Bis-substituted quinazoline-based compounds showed appreciable drug-like characteristics and can be developed as potent anticancer agents.
合成了12种基于2,4-双取代喹唑啉的化合物，并对其抗增殖和增强微管蛋白聚合的潜力进行了筛选。在该系列中，被咪唑环取代的化合物A4V-3对MCF-7、HCT-116和SHSY-5Y癌细胞的IC值分别为4.25 μM、2.65 μM和9.95 μM，而被苯并三唑取代的A4V-5的IC值分别为3.45 μM、7.25 μM和8.14 μM。在涉及细胞周期分析、凋亡检测和JC-1研究的机制研究中，发现化合物A4V-3可使细胞停滞在细胞周期的G/M期并诱导线粒体介导的凋亡。此外，化合物A4V-3显示出显著的增强微管蛋白聚合的潜力。基于2,4-双取代喹唑啉的化合物表现出可观的类药物特性，可开发成为有效的抗癌药物。
